The effect of fentanyl, DNQX and MK‐801 on dorsal horn neurones responsive to colorectal distension in the anaesthetized rat

Kozlowski, Christopher; Bountra, C; Grundy, David

doi:10.1046/j.1365-2982.2000.00205.x

Cited by 16 publications

(17 citation statements)

References 34 publications

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“…Other investigators have shown that in naïve, adult rats without hyperalgesia, the AMPA receptor antagonist CNQX, differentially modified the activity of these two classes of neurons based on graded intensities of colon distension, having some effect on SL-A neurons (Ji and Traub, 2002). Another study in adult, naïve rats, demonstrated that the AMPA receptor antagonist DNQX, and not the NMDAR antagonist MK-801, decreased the responses of SL-A spinal neurons to CRD (Kozlowski et al, 2000). However, in a model of urinary bladder distension (Catroman and Ness 2002), three clinically available NMDAR antagonists (ketamine, dextromethorphan, and memantine) all demonstrated an inhibitory effect only on type I spinal neurons and not type II.…”

Section: Discussionmentioning

confidence: 99%

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NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

Miranda

Mickle

Bruckert

et al. 2014

European Journal of Pharmacology

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NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD >20mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life.

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Section: Discussionmentioning

confidence: 99%

“…Others have reported a similar effect on SL-S neurons in a model of visceral hyperalgesia induced by acute inflammation of the colon (Ness and Gebhart, 2000). It has also been suggested that these subtypes of neurons respond differently to pharmacological intervention (Ji and Traub 2002; Kozlowski et al, 2000). …”

Section: Introductionmentioning

confidence: 99%

NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

Miranda

Mickle

Bruckert

et al. 2014

European Journal of Pharmacology

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“…Distension pressures of 10, 20, 40, 60 and 80 mmHg were routinely performed with 1 min between each stimulus. Responses were classified according to established criteria 2 , 4 . Isobaric, rather than isovolumetric stimuli were used to avoid mistaking genuine changes in response during bile infusion for changes in colonic wall compliance.…”

Section: Methodsmentioning

confidence: 99%

“…A considerable degree of processing occurs in the dorsal horn before information is directed to areas of the brain via ascending tracts in the dorsal and lateral spinal white matter 2 , 3 . Understanding of the pharmacology of this pathway has emerged recently 4 . Emphasis has been placed on processing of nociceptive mechanosensory afferent input.…”

Section: Introductionmentioning

confidence: 99%

Colonic mechanoreceptor inputs to rat lumbo‐sacral dorsal horn neurones: distribution, thresholds and chemosensory modulation

Andrew

Blackshaw

2001

Neurogastroenterology Motil

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In order to better understand the central processing of visceral sensory information, we studied the responses of lumbo-sacral dorsal horn (L4-S1) neurones to colonic stimuli in anaesthetized rats. Twenty-four neurones responded to distal colonic distension with a 2.5-cm balloon; six of these were tested with proximal colonic distension, to which none responded. All neurones tested responded to somatic non-noxious inputs (tail movement). Responses to colonic distension were excitatory (n=22) or inhibitory (n=2). Sixteen neurones responded at a threshold of 20 mmHg or less, five at 20-40 mmHg, and three at 40-80 mmHg. Three of 10 neurones tested showed increased responses to colonic distension after intraluminal perfusion with bile. Bile itself did not evoke a response. We conclude that lumbo-sacral spinal neurones selectively receive mechanosensory inputs from the distal colon. Neurones respond at thresholds within and above the physiological range. Dorsal horn neurones receiving colonic mechanosensory inputs are not directly modulated by chemosensory inputs, but their responsiveness to distension may be augmented.

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“…In the rat, the NMDA glutamate receptor subtype is involved in a lumbosacral inhibitory mechanism controlling bladder activity (36,38), whereas the AMPA-kainate subtype controls 1) the activation of spinal neurons induced by colorectal distension (16) and 2) the frequency of spontaneous and perineal stimulation-evoked bladder contractions (36). Thus NMDA and AMPA-kainate receptors participate to the spinal control of pelvic organs.…”

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confidence: 99%

Spinal control of erection by glutamate in rats

Rampin¹,

Monnerie²,

Jerome³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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/ ajpregu.00645.2003.-The lumbosacral spinal network controlling penile erection is activated by information from peripheral and supraspinal origins. We tested the hypothesis that glutamate, released by sensory afferents from the genitals, activates this proerectile network. In anesthetized intact and T8 spinalized (i.e., freed from supraspinal inhibition) male rats, the parameters of electrical stimulation of the dorsal penile nerve (DPN) that elicited intracavernous pressure (ICP) rises were determined. In T8 spinalized rats, DPN stimulations were applied in the presence of D(Ϫ)-2-amino-5-phosphonopentanoic acid (D-AP5), a competitive NMDA receptor antagonist, or of 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX), an AMPA-kainate receptor antagonist, injected intrathecally at the lumbosacral level. Both antagonists, alone or in combination, dose dependently decreased the ICP rise and increased its latency. In conscious rats, reflexive erections were depressed by D-AP5 and NBQX, as revealed by an increased latency of the first erection and by decreases of the number of rats displaying erections, of the number of erection clusters and of the number of erections per cluster. In anesthetized rats, the combined administration of the glutamatergic agonists NMDA and AMPA elicited ICP rises in the absence of DPN stimulation. In contrast, both agonists moderately decreased the ICP rise elicited by DPN stimulation but did not affect its latency. These results support our hypothesis that glutamate, released on stimulation of the genitals and acting at AMPA and NMDA receptors, is a potent activator of the spinal proerectile network. urogenital; sexual reflexes; lumbosacral spinal cord ERECTION IS CAUSED by the simultaneous increase of blood flow to the penis and active relaxation of the erectile tissue of the corpora cavernosa and the corpus spongiosum (1). Both mechanisms are controlled by the autonomic nervous system.In conscious rats, retraction of the penile sheath elicits reflexive erections (14, 32) that are accompanied by penile pressure rises (5, 33). In anesthetized rats, intracavernous pressure (ICP) rises are reflexively elicited by stimulation of the dorsal penile nerve (DPN) (27,29,35). Reflexive erections rely on a reflex loop that includes a network of lumbosacral spinal neurons as a link between the DPN as the afferent limb and the sacral parasympathetic outflow as the efferent limb. The DPN conveys sensory information from the penis and perigenital skin to the lumbosacral cord (23, 26). Its stimulation activates a network of lumbosacral neurons (30). In rats, the proerectile parasympathetic outflow originates in the sacral parasympathetic nucleus (SPN) of the L6-S1 spinal cord (28). The SPN contains the preganglionic neurons that innervate the penis (21). The neurotransmitters that activate the spinal proerectile network are presently unknown.The role of glutamate in the spinal control of the urinary and the lower digestive tracts has been established. In the rat, the NMDA gl...

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The effect of fentanyl, DNQX and MK‐801 on dorsal horn neurones responsive to colorectal distension in the anaesthetized rat

Cited by 16 publications

References 34 publications

NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

Colonic mechanoreceptor inputs to rat lumbo‐sacral dorsal horn neurones: distribution, thresholds and chemosensory modulation

Spinal control of erection by glutamate in rats

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